NEW YORK (Reuters Health) - The PREVAIL trial of enzalutamide (Xtandi, Medivation and Astellas Pharma) showed the efficacy of the agent in chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). New examination of the data by multinational investigators confirms its benefit across subgroups.
As Dr. Christopher P. Evans told Reuters Health by email, "The subset analysis of PREVAIL is consistent with the initial report and validates enzalutamide across the castration-resistant prostate cancer disease spectrum of location and extent of disease."
In a March 20 online paper in European Urology, Dr. Evans, of the University of California, Davis, School of Medicine, Sacramento, and colleagues note that in the PREVAIL study asymptomatic or minimally symptomatic patients were randomized to enzalutamide or placebo while continuing androgen deprivation therapy.
In the current analysis, the researchers specifically examined data by subgroup. This included 1,513 participants with nonvisceral disease, 204 with visceral disease, 867 with fewer than four bone metastases (low-volume bone disease), 850 with four or more bone metastases (high-volume bone disease) and 195 with lymph node-only disease.
Compared to placebo, enzalutamide improved radiographic progression-free survival in patients with nonvisceral disease (hazard ratio 0.18) and visceral disease (HR 0.28). This was also true in low- or high-volume bone disease (HR 0.16 and 0.22) and in lymph node only disease (HR 0.09).
For overall survival, the hazard ratio was below 1 across all disease subgroups and the agent was well tolerated in patients with or without visceral disease. The incidence of adverse events leading to discontinuation of the agent was low (6%) in both of these subgroups.
The results, the researchers concluded, "suggest that enzalutamide is an active treatment in this prostate cancer population, irrespective of the location and extent of baseline disease."
Commenting on the findings by email, Dr. James L. Mohler of Roswell Park Cancer Institute, New York, told Reuters Health, "The benefits observed with enzalutamide compared to placebo across all CRPC subgroups confirm that prostate cancer remains androgen-sensitive probably due to its ability to produce testicular androgens by intratumoral, intracrine androgen metabolism."
However, Dr. Mohler, who is chair of the department of urology, and professor of oncology, added that "the extension of overall survival, though not yet defined, appears relatively short and all efforts should be focused on developing even better treatments for CRCP once established, or better yet, slowing its development."
The study was supported by Medivation and Astellas Pharma. Dr. Evans has acted a consultant for and received research funding from these and other companies. Other authors have such relationships. A number are employees of Medivation and one worked for Astellas at the time of the study.
Eur Urol 2016.